rs773800797

Variant names:

• chr1-229326844-A-C
• rs773800797
• NM_145257.5:c.530T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-229326844-A-C
• chr1-229326844-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145257.5(CCSAP):​c.530T>G​(p.Ile177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I177T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

CCSAP (HGNC:29578): (centriole, cilia and spindle associated protein) Enables microtubule binding activity. Involved in mitotic spindle microtubule depolymerization and regulation of mitotic spindle assembly. Located in axon; ciliary transition zone; and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22050175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSAP	NM_145257.5	c.530T>G	p.Ile177Arg	missense_variant	Exon 3 of 4	ENST00000284617.7	NP_660300.3
CCSAP	NM_001410936.1	c.188T>G	p.Ile63Arg	missense_variant	Exon 2 of 3		NP_001397865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCSAP	ENST00000284617.7	c.530T>G	p.Ile177Arg	missense_variant	Exon 3 of 4	1	NM_145257.5	ENSP00000284617.2
CCSAP	ENST00000366687.5	c.530T>G	p.Ile177Arg	missense_variant	Exon 2 of 3	1		ENSP00000355648.1
CCSAP	ENST00000483092.1	n.1513T>G		non_coding_transcript_exon_variant	Exon 3 of 4	1
CCSAP	ENST00000366686.1	c.188T>G	p.Ile63Arg	missense_variant	Exon 2 of 3	2		ENSP00000355647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.078	T;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.16
Sift	Benign	0.057	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.35
MutPred		0.30		Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);.;
MVP		0.36
MPC		1.7
ClinPred		0.81	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.095

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs773800797; hg19: chr1-229462591;